L-Amino acids, in particular L-threonine, are used in human medicine and in the pharmaceutical industry, in the food industry and very particularly in animal nutrition.
It is known that L-amino acids are produced by fermentation of strains of the Enterobacteriaceae, in particular Escherichia coli (E. coli) and Serratia marcescens. Because of the great importance, work is, continuously being carried out on the improvement of the production methods. Method improvements can relate to fermentation measures, such as, for example, agitation and supply with oxygen, or the composition of the nutrient media, such as, for example, the sugar concentration during the fermentation, or the workup to give the product form, by, for example, ion-exchange chromatography, or the intrinsic performance properties of the microorganism itself.
To improve the performance properties of these microorganisms, methods of mutagenesis, selection and mutant selection are employed. In this manner strains are obtained which are resistant to antimetabolites such as, for example, the threonine analog α-amino-β-hydroxyvaleric acid (AHV) or are auxotrophic for metabolites of importance in regulation and produce L-amino acids such as, for example L-threonine.
For some years, likewise methods of recombinant DNA technology have been used for strain improvement of L-amino acid-producing strains of the family Enterobacteriaceae, by amplifying individual amino acid biosynthesis genes and studying the effect on production. Summarizing information on cell and molecular biology of Escherichia coli and Salmonella is to be found in Neidhardt (ed): Escherichia coli and Salmonella, Cellular and Molecular Biology, 2nd edition, ASM Press, Washington, D.C., USA, (1996).